Upregulation of the angiogenic factors PlGF, VEGF and their receptors (Flt-1, Flk-1/KDR) by TSH in cultured thyrocytes and in the thyroid gland of thiouracil-fed rats suggest a TSH-dependent paracrine mechanism for goiter hypervascularization

Giuseppe Viglietto, Annunciata Romano, Giovanni Manzo, Gennaro Chiappetta, Iole Paoletti, Daniela Califano, Maria Giulia Galati, Valeria Mauriello, Paola Bruni, Carmine T. Lago, Alfredo Fusco, M. Graziella Persico

Research output: Contribution to journalArticlepeer-review

Abstract

Placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) represent two closely related angiogenic growth factors active as homodimers or heterodimers. Since goiters of the thyroid gland are extremely hypervascular, we investigated the expression of PlGF, VEGF and their receptors, Flt-1 and Flk-1/KDR, in a small panel of human goiters from patients with Graves's disease, in an animal model of thyroid goitrogenesis and in in vitro cultured thyroid cells. Here we report that the mRNA expression of PlGF, VEGF and their receptors is markedly enhanced in biopsies of goiters resected from Graves's patients. In vivo studies demonstrated that in the thyroid gland of thiouracil-fed rats, increased mRNA and protein expression of PlGF, VEGF, Flt-1 and Flk-1/KDR occurred subsequent to the rise in the serum thyroid stimulating hormone (TSH) levels and in parallel with thyroid capillary proliferation. In vitro studies confirmed the existence of such TSH-dependent paracrine communication between thyroid epithelial cells and endothelium since the conditioned medium collected from TSH-stimulated thyrocytes acquired mitogenic activity for human umbilical vein endothelial (HUVE) cells. Altogether, these data suggest that PlGF and VEGF, released by thyrocytes in response to the chronic activation of the TSH receptor pathway, may act through a paracrine mechanism on thyroid endothelium.

Original languageEnglish
Pages (from-to)2687-2698
Number of pages12
JournalOncogene
Volume15
Issue number22
Publication statusPublished - 1997

Keywords

  • Hypervascularization
  • PlGF
  • Thyroid goiter
  • TSH
  • VEGF

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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